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Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 1043 1050

www.elsevier.com/locate/pnpbp

A continuity between bipolar II depression and major


depressive disorder?
Franco Benazzi
Hecker Psychiatry Research Center, Forli, Italy
University of California at San Diego (USA) Collaborating Center, United States
Department of Psychiatry, University of Szeged, Szeged, Hungary
Department of Psychiatry, National Health Service, Forli, Italy
Available online 8 May 2006

Abstract

Background: A recent series of studies has questioned the current categorical split of mood disorders into bipolar and depressive disorders. Mixed
states, especially mixed depression (i.e., depression plus co-occurring, noneuphoric, hypomanic symptoms) might support a continuity between
bipolar II (BP-II) depression and major depressive disorder (MDD). The aim of the study was to assess the distribution of intradepressive
hypomanic symptoms rating between BP-II and MDD depressions. A bi-modal distribution would support a categorical distinction, and no bi-
modality would support continuity.
Methods: Consecutive 389 BP-II and 261 MDD major depressive episode (MDE) outpatients were interviewed (off psychoactive drugs) with the
Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide (HIG, to assess intradepressive hypomanic symptoms), and the Family
History Screen, by a mood specialist psychiatrist in a private practice. Mixed depression was defined as MDE plus 3 or more intradepressive,
noneuphoric hypomanic symptoms, a definition validated by Akiskal and Benazzi. The distribution of intradepressive hypomanic symptoms
rating was studied by Kernel density estimate and by histogram.
Results: BP-II depression, versus MDD depression, had significantly lower age at onset, was significantly more likely to be atypical and mixed,
had more depression recurrences, and a higher bipolar family history loading. BP-II depression, versus MDD depression, had significantly more
irritability, racing/crowded thoughts, distractibility, psychomotor agitation, talkativeness, increased goal-directed activity, and excessive risky
activities. HIG scores were significantly higher in BP-II. The distribution of intradepressive hypomanic symptoms rating showed no bi-modality in
the entire depression sample.
Conclusions: Interpretation of study findings relies on the method used to define a categorical disorder. By using classic diagnostic validators
(such as family history and age at onset), BP-II and MDD depressions would seem to be distinct disorders. Instead, by using the bi-modality
approach, a continuity would seem to be supported. Which of these methods for classification is the best has yet to be shown.
2006 Elsevier Inc. All rights reserved.

Keywords: Bipolar disorder; Bipolar II disorder; Continuity; Major depressive disorder; Spectrum

1. Introduction

The current diagnostic systems split mood disorders categori-


Abbreviations: BP-I, bipolar I disorder; BP-II, bipolar II disorder; DSM-IV- cally into bipolar and depressive disorders (DSM-IV-TR, Diag-
TR, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
Text-Revised; GAF, Global Assessment of Functioning scale; HIG, Hypomania
nostic and Statistical Manual of Mental Disorders, Fourth Edition,
Interview Guide; ICD-10, International Classification of Diseases, Tenth Text-Revised, American Psychiatric Association, 2000; ICD-10,
Edition; MDD, major depressive disorder; MDE, major depressive episode; International Classification of Diseases, Tenth Edition, World
nc, not calculable; OR, Odds Ratio; SCID-CV, Structured Clinical Interview for Health Organization, 1992). Recent studies have instead supported
DSM-IV Axis I DisordersClinician Version; YMRS, Young Mania Rating a continuity/spectrum of mood disorders, including overlapping
Scale; 95% CI, 95% Confidence Interval.
Via Pozzetto 17, 48015 Castiglione di Cervia RA, Italy. Tel.: +39 335 6191 and dimensional disorders ranging from bipolar I (BP-I) and bipolar
852; fax: +39 054 330 069. II (BP-II) disorders to major depressive disorder (MDD) (Angst
E-mail address: FrancoBenazzi@FBenazzi.it. et al., 2003; Akiskal, 2003; Cassano et al., 2004; Dunner, 2003).
0278-5846/$ - see front matter 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.pnpbp.2006.03.037
1044 F. Benazzi / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 10431050

According to Kraepelin (1921), the mood disorders he united in his Maj et al., 2003; Maj et al., in press; Mantere et al., 2004; Sato et al.,
manic-depressive insanity had a common root with gradual 2003, 2005). The depressive mixed states (mixed depression)
transitions between the individual forms, were without sharp described by Kraepelin (1921) included the same symptoms found
boundaries, and delimitation of individual clinical forms of the in modern studies. The manic foundation of mild depressive
malady was wholly artificial and arbitrary. mixed states (corresponding to those seen in the study setting) was
Some features supporting a continuity/spectrum of mood indicated by slight flight of ideas, restlessness, talkativeness, and
disorders may be the following: 1) mixed states (especially mixed irritability (p 112). Kraepelin described a grading of the severity of
depression), because of the combination of opposite polarity the thought disorders of hypomania, including crowded thoughts,
symptoms in the same episode, 2) MDD found to be the most described as non-stop thoughts filling the mind.
common mood disorder in relatives of bipolar probands (Duffy Frequency of mixed depression, defined as a major depressive
et al., 2000), 3) MDD found to have low diagnostic stability episode (MDE) plus at least 2 or 3 intradepressive manic/hypo-
(Angst et al., 2005a; Goldberg et al., 2001), 4) many lifetime manic symptoms, was up to 70% in BP-I and BP-II, and up to 30%
manic/hypomanic symptoms found in MDD (Cassano et al., in MDD.
2004), showing no bi-modal distribution (Cassano et al., 2002)
and 5) correlation found between lifetime manic/hypomanic 1.2. Study aim
symptoms and current depressive symptoms in MDD (Cassano
et al., 2004). The study's aim was to find if there was a continuity (i.e., no bi-
Instead, some features supporting a categorical distinction modality) between BP-II depression and MDD depression. In order
between bipolar and depressive disorders may be the following: to do this testing, the distribution of hypomanic symptoms rating
differences on 1) family history (Coryell, 1999; Duffy et al., 2000), between BP-II and MDD depressions was assessed.
2) age at onset (McMahon et al., 1994), 3) gender (Winokur et al.,
1993a,b; Winokur et al., 1995), 3) clinical picture of BP-I depres- 2. Methods
sion versus MDD depression (Mitchell and Malhi, 2004) and 4)
course of illness (Winokur et al., 1993a,b, 1995). 2.1. Study setting
According to Kendell and Jablensky (2003), finding a bi-modal
distribution of distinguishing, cross-sectional symptoms between The setting of the study is an outpatient psychiatry private
two related syndromes would support a categorical distinction. BP- practice in Emilia-Romagna region, northern Italy. This setting is
II is the closest of the bipolar disorders to MDD, and it could be the more representative of the mood disorders usually seen in
one to be compared to MDD. The cross-sectional symptoms to psychiatric clinical practice in this area (apart from the psychotic
study should be symptoms distinguishing the two depressive ones) because 1) it is the first or second (after general practitioners)
syndromes. BP-II depression, versus MDD depression, was found line of treatment of mood disorders, 2) the most severe and socially
to have more concurrent DSM-IV-TR hypomanic symptoms (i.e., disadvantaged individuals are usually seen in tertiary-care centers
to be more likely to be a mixed depression). According to Kraepelin (i.e., national health services and academic centers), 3) mood
(1921), mixed states were one of the main building blocks of his disorder patients do not like to be treated in the national health
unitary view of mood disorders. Finding a bi-modal distribution of services for fear of stigma, and 4) most individuals can afford a
the intradepressive hypomanic symptoms rating between BP-II and private psychiatrist (fee-for-service) in this area, reducing a possible
MDD depressions could support a categorical distinction, while income bias.
finding no bi-modality could support a continuity.
2.2. Interviewer
1.1. Mixed depression
The interviewer of the study was a senior clinical (21 years in
Mixed depression is the combination of depression and manic/ practice) and research mood disorder specialist psychiatrist.
hypomanic symptoms, not including elevated mood by definition.
It is not present in DSM-IV-TR. Apart from the classic descriptions 2.3. Patient population
by Kraepelin (1921), in modern times mixed depression has been
repeatedly described in BP-I, BP-II, and MDD (Abrams and Taylor, Consecutive 389 BP-II and 261 MDD outpatients, presenting
1980; Andreasen and Grove, 1982; Akiskal, 1996; Akiskal and voluntarily (i.e., self-referred, apart from a small number referred by
Benazzi, 2003; Benazzi, 2005a,b; Biondi et al., 2005; Himmelhoch general practitioners) for major depressive episode (MDE)
et al., 1976a,b; Koukopoulos and Koukopoulos, 1999; Perugi et al., treatment, were included in the last 6 years. Substance-related
2001; Maj et al., 2003; Mantere et al., 2004; Sato et al., 2003; disorders and borderline personality disorder were excluded
Raskin et al., 1969). because these disorders may confound the diagnosis of BP-II and
The most frequent DSM-IV-TR manic/hypomanic symptoms of mixed states due to their high background mood instability
mixed depression were irritability, mental overactivity (flight of (Akiskal and Pinto, 1999). Anyway, these disorders are rare in the
ideas, racing thoughts, crowded thoughts), and motor overactivity study setting (Benazzi, 2000). Clinically significant general
(psychomotor agitation, more talkativeness) (Akiskal, 1996; medical illnesses and cognitive disorders were also excluded. Pa-
Akiskal and Benazzi, 2003; Benazzi, 2005a,b; Biondi et al., tients had to present off psychoactive drugs for at least 2 weeks
2005; Koukopoulos and Koukopoulos, 1999; Perugi et al., 2001; (apart from a few individuals on small doses of benzodiazepines),
F. Benazzi / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 10431050 1045

in order to exclude patients with drug-induced or drug-suppressed which had lower scores than BP-I and BP-II. The total score
intradepressive hypomanic symptoms. Informed consent was correctly classified as MDD or BP 91% of the patients. Its reported
obtained by all patients, as the interview's questions are part of inter-rater reliability is k= 0.88, total score range is 0 to 60, item
the usual clinical assessment of each new patient in the study score range is 0 to 4 (Williams et al., 1994).
setting. The Italian law does not require further steps for a study like
the present one. 2.6. Interview methods

2.4. Assessment instruments Systematic data gathering are part of the clinical routine in the
study setting. Systematic interviews about history of hypomanic
All diagnostic procedure and instruments described represent and manic episodes were always conducted soon after the diagnosis
the systematic clinical routine of the author. During the first visit of MDE and before the assessment of study variables, in order to
(when presenting for the first time), the following instruments were avoid a possible bias related to knowledge of bipolar signs (Ghaemi
used in a cross-sectional assessment: et al., 2002). It is well known that patients do not report spon-
taneously about past hypomanic episodes, because hypomanic
1) the Structured Clinical Interview for DSM-IV Axis I Dis- episodes are often pleasant periods of improved functioning and/or
ordersClinician Version (First et al., 1997) (SCID-CV, periods without marked impairment. Indeed, patients even view
reported inter-rater reliability k= 0.701.0), as modified by hypomania as a state of real self-normality which they hope will
Benazzi and Akiskal (described below) to improve the probing last as much as possible. The key informants often present during
for BP-II (Akiskal and Benazzi, 2005; Benazzi and Akiskal, the interview were therefore very helpful in supporting a diagnosis
2003); the question on racing thoughts was supplemented by of past hypomania, as they could remember the change in func-
Kraepelin's (1921) description of crowded thoughts: the tioning associated with hypomania. The SCID-CV is partly semi-
patients complain that they have so many thoughts in their structured and based on clinical evaluation (not on simple yes/no
head, they have no settled thoughts (p 14), a patient complains answers to structured questions). Wording of the sentences can be
that he must meditate so much, that fresh thoughts are always changed to improve and to check the understanding of the inter-
coming to him, that he has too much in his head, that he finds no viewee. This is an important advantage versus fully structured
rest (p 75), patients cannot hold fast their thoughts at all, interviews, because this interview method has been shown to
constantly things come crowding into their head (pp 107108); reduce the false negative mood disorders, especially BP-II (Aalto-
in DSM-IV-TR, only racing thoughts are reported, defined by Setala et al., 2002; Benazzi, 2003b; Brugha et al., 2001; Dunner and
speedy thinking, and by rapid jumping of thinking in the more Tay, 1993; Simpson et al., 2002). The skip out instruction of the
severe states; stem question on history of mood changes (elevated/irritable mood)
2) the Global Assessment of Functioning scale (GAF, in the SCID- was not followed, because a negative answer would force to shift
CV) for assessing MDE severity; the interview to nonbipolar disorders. A period of elevated or
3) the Hypomania Interview Guide (HIG) (Williams et al., 1994) to irritable mood can be seen as normality by patients (everybody has
better assess intradepression hypomanic symptoms; ups and downs), while asking about a period of much elevated or
4) the Family History Screen (Weissman et al., 2000) (reported irritable mood can be easily seen as a sign of a severe mental
inter-rater reliability k= 0.85) for assessing Bipolar (type I and disorder and soon denied. This is one of the reasons why some
type II) family history in probands' first-degree relatives. researchers have been focusing the interview more on history of
overactivity (increased goal-directed activity) (Akiskal and Be-
The interviewer's inter-rater reliability k for the diagnosis of BP- nazzi, 2005; Angst et al., 2003; Benazzi, 2003b). It was so possible
II had been previously tested versus a psychiatrist trained in bipolar to assess all past hypomanic symptoms by not following the skip
disorders, and found to be 0.73 (Benazzi, 2003a). This k statistics is out instruction of the SCID-CV stem question. This approach
similar to that found using similar interview methods by trained followed previous reports showing the diagnostic utility of a
clinicians in genetic investigations (Simpson et al., 2002). probing for history of hypomania more focused on overactivity
Often, family members or close friends supplemented clinical than on mood changes (Akiskal and Benazzi, 2005; Angst et al.,
information during the interview, increasing the validity of the 2003; Benazzi, 2003b; Dunner and Tay, 1993; Simpson et al.,
diagnosis of BP-II and of the family history (American Psychiatric 2002). Overactivity (the most striking feature of hypomania,
Association, 2000). according to Kraepelin, 1921) is an observable behavior easier to
remember than mood changes. Mood changes were always
2.5. The Hypomania Interview Guide (HIG) required for the diagnosis of BP-II (American Psychiatric Asso-
ciation, 2000), and were more easily remembered after remember-
The Hypomania Interview Guide (HIG) (Williams et al., 1994) ing overactivity. In order to carefully assess history of overactivity,
was the basic instrument used in the present study. The HIG it was always requested that patients described the periods of
assesses all DSM-IV-TR hypomanic symptoms better than the overactivity (by giving examples), to know if the patient had
YMRS (Young Mania Rating Scale) (Young et al., 1978), which correctly understood the meaning of the questions on overactivity
has several items biased toward inpatient mania. It was validated in (e.g., increase in efficiency, accomplishments, creativity, planning
BP-I, BP-II and MDD (Goel et al., 1999). The HIG showed high of, and participation in, multiple activities, often creative and
internal consistency. Normal controls had lower scores than MDD, productive, increased sociability, increased sexual activity, with or
1046 F. Benazzi / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 10431050

Table 1 compared to hypomania (required for BP-II diagnosis). Instead, in


Sample features the present study a lot of effort was made to diagnose hypomania in
Variables: mean (SD), % BP-II MDD OR (95% CI) the relatives (Akiskal and Benazzi, 2005).
n = 389 n = 261 Mixed depression (depressive mixed state) was defined as MDE
Age, years 41.3 (12.9) 46.8 (14.8) 0.7 (0.60.8) (depression) plus 3 or more co-occurring, intradepressive DSM-IV-
Age at onset first MDE 22.8 (10.6) 31.8 (13.8) 0.5 (0.40.6) TR hypomanic symptoms (elevated mood and increased self-
Females 67.0 61.6 1.2 (0.91.7)
esteem were always absent by definition), a definition validated by
N=5 MDEs 78.9 58.2 2.6 (1.83.7)
MDE symptoms N2 years 37.5 34.8 1.1 (0.81.5) clinical, family history, and psychometric validators by Akiskal and
Axis I comorbidity 54.2 47.5 1.3 (0.91.7) Benazzi (2003), and by Benazzi (2005b). Other authors require 2 or
Psychotic features 7.7 8.4 0.9 (0.51.6) more intradepressive hypomanic symptoms (Bauer et al., 2005;
Melancholic features 12.0 13.0 0.9 (0.51.4) Sato et al., 2003), but the definition of mixed depression used in the
Atypical depression 52.6 28.7 2.7 (1.93.8)
present study is the most validated. The noneuphoric hypomanic
Mixed depression 64.5 32.1 3.8 (2.75.3)
GAF 50.2 (9.2) 50.9 (9.6) 0.9 (0.81.0) symptoms had to appear during the MDE (i.e., a hypomanic
Bipolar (type I + type II) 44.7 15.3 4.4 (2.87.0) symptom-free interval of at least one month before the MDE was
family history required), to last at least one week, and to be present at the time of
Bipolar-II disorder (BP-II) versus major depressive disorder (MDD), by the interview (to increase validity).
univariate logistic regression. Atypical depression was defined, according to DSM-IV-TR
MDE = major depressive episode; Mixed Depression = MDE plus N = 3 criteria, as an MDE presenting the atypical features specifier.
intradepressive hypomanic symptoms; GAF = Global Assessment of Function-
ing scale; OR = Odds Ratio; 95% CI = 95% Confidence Interval; p b 0.05;
p b 0.01. 2.8. Testing the study's aim

To find if BP-II depression and MDD depression were distinct


without mild impairment of functioning, a clear change in func- categories, or were instead overlapping disorders along a
tioning compared to the usual self). If the patient did not remember continuum, Kendell and Jablensky's (2003) method was
periods of overactivity and mood changes, it was asked how were followed, by looking for a bi-modality in the distribution of the
his/her mood and behavior in spring and summer compared to HIG rating of the intradepressive hypomanic symptoms between
winter, how were his/her mood and behavior soon after/before a the depressive syndromes (MDE) of BP-II and MDD. Intrade-
depression, and soon after skipping a night sleep (these are further pressive hypomanic symptoms were chosen because these
probes likely to show periods of overactivity, if present). symptoms were reported to be much more common in BP-II
versus MDD depressive syndromes (Akiskal and Benazzi, 2003;
2.7. Hypomania duration Benazzi, 2005a; Bauer et al., 2005; Henry et al., 2005; Maj et al.,
in press; Mantere et al., 2004; Sato et al., 2003), and because
A minimum duration of hypomania of 2 days was required mixed states would support, according to Kraepelin (1921), a lack
(instead, DSM-IV-TR requires a minimum duration of 4 days), on of boundaries between mood disorders. If BP-II depression were a
the basis of data supporting this cutoff, i.e., no differences on category distinct from MDD depression, the distribution of the
diagnostic validators between BP-II with history of hypomania HIG rating should have shown a bi-modality between the two
lasting less than 4 days, and DSM-IV-TR BP-II (Angst et al.,
2003; Benazzi, 2001; Benazzi and Akiskal, in press; Judd et al.,
2003), while DSM-IV-TR cutoff is not data-based (Dunner, Table 2
2003). Among the present study BP-II, around 30% met this 2- Intradepressive hypomanic symptoms in bipolar-II depression (BP-II) versus
day cutoff for hypomania. Therefore, the frequency of DSM-IV- major depressive disorder (MDD) depression, by univariate logistic regression
TR BP-II in the present sample was around 40%, a frequency very Variables: %, mean (SD) BP-II MDD OR (95% CI)
close to that found in other outpatient sample studies (Dunner and n = 389 n = 261
Tay, 1993; Hantouche et al., 1998; Manning et al., 1999; Elevated mood 0.0 0.0 nc
Rybakowski et al., 2005; Smith et al., 2005). Irritable mood 61.6 34.8 3.0 (2.14.1)
Recurrences were defined as recurrences of MDE, as Inflated self-esteem, grandiosity 0.0 0.0 nc
Decreased need for sleep 1.5 0.0 nc
hypomanic episodes are more difficult to count, partly because
More talkative than usual 24.6 9.5 3.0 (1.94.9)
hypomanic episodes are often not seen as abnormal periods by Racing/crowded thoughts 75.3 54.7 2.6 (1.93.7)
patients, partly because hypomania duration may be brief (Angst Distractibility 78.9 65.1 1.9 (1.32.7)
et al., 2003; Benazzi and Akiskal, in press). Recurrences were Increase in goal-directed activity 7.7 0.7 10.8 (2.545.6)
categorically divided by a cutoff of 5 episodes, because 5 or more Psychomotor agitation 35.9 17.6 2.6 (1.73.8)
Excessive risky activities 19.5 6.5 3.4 (2.06.0)
episodes was shown to identify highly recurrent mood disorders
N hypomanic symptoms 3.0 (1.4) 1.8 (1.2) 1.9 (1.62.2)
(Kessing et al., 2004). Hypomania Interview Guide 8.5 (3.7) 5.3 (3.2) 1.2 (1.21.3)
Bipolar disorders family history included history of BP-I and (HIG) score
BP-II in proband's first-degree relatives. Usually, only BP-I family HIG median 8 6 z = 8.6
history is studied, because mania (which is often psychotic, and HIG = Hypomania Interview Guide; OR = Odds Ratio; 95% CI= 95%
often requires hospital care) is simpler to diagnose by history Confidence Interval; p b 0.05; p b 0.01; nc = not calculable.
F. Benazzi / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 10431050 1047

.1
.08
.06
Density
.04
.02
0

0 5 10 15 20 25
HIG

Kernel density estimate


Normal density

Fig. 1. Kernel density estimate (a normal curve is superimposed) of the Hypomania Interview Guide (HIG) scores of intradepressive hypomanic symptoms in the
combined bipolar-II disorder plus major depressive disorder depression sample.

depressive syndromes, while no bi-modality would have sup- nonparametric histogram smoothers which can reveal skewness
ported a continuity. and multi-modality. Disadvantages of the histogram method are
that it is parametric, and that the fixed bin width results in
2.9. Data analysis disproportional representation of density at the center and in the
tails of the distribution. The Kernel density estimate overcomes
The distribution of the HIG rating was studied by univariate the limitations of the histogram method and can better evaluate
Kernel density estimation, and by histogram. Normality of the multi-modality. For an overview of the Kernel density estimate,
Kernel density estimation curve was also checked. While histo- see Salgado-Ugarte et al. (1994).
grams provide accurate pictures of categorical variables, smooth Logistic regression was used to study associations. Medians
density functions (Kernel estimators) are better to represent were compared by the MannWhitney test. STATA Statistical
noncategorical variables. Kernel estimators can be regarded as Software, Release 8.2, was used (Stata Corporation, College
.1
.08
.06
Density
.04 .02
0

0 5 10 15 20 25
HIG

Fig. 2. Histogram of the Hypomania Interview Guide (HIG) scores of intradepressive hypomanic symptoms between bipolar-II depression and major depressive
disorder depression.
1048 F. Benazzi / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 10431050

Station, TX, USA, 2003). P values were two-tailed, and alpha The distribution of the scores of the intradepression
level was set at 0.01, to correct for multiple comparisons (Alt- hypomanic symptoms was expected to be bi-modal, because
man et al., 2000). of the differences in the frequency of these symptoms between
BP-II and MDD depressions. Instead, in the present study it was
3. Results shown that intradepression hypomanic symptoms rating had no
bi-modality, supporting a continuity between BP-II and MDD
Comparisons between BP-II and MDD are presented in depressions. The lack of bi-modality in the distribution of the
Table 1. BP-II depression, versus MDD depression, had intradepression hypomanic symptoms rating between BP-II and
significantly lower age and age at onset, was significantly MDD found in the present study is mirrored by a similar, non-
more likely to be atypical and mixed, had more depression bi-modal, distribution of lifetime manic/hypomanic symptoms
recurrences, and had a higher bipolar family history loading. in BP-I and MDD, and of the intramania depressive symptoms
Table 2 shows the comparison of the intradepressive (Bauer et al., 2005; Cassano et al., 2002). These studies com-
hypomanic symptoms between BP-II and MDD depressions. plement and support each other.
BP-II had significantly more irritability, racing/crowded
thoughts, distractibility, psychomotor agitation, talkativeness, 4.3. Interpretation
increased goal-directed activity, and excessive involvement in
pleasurable activities. The mean and median HIG scores were Interpretation of study findings relies on the method used to
significantly higher in BP-II. The modal item scores were 2 to 3 define a categorical disorder. By using classic diagnostic
for the most common symptoms (irritability, racing/crowded validators, BP-II and MDD depressions would seem to be
thoughts, distractibility, psychomotor agitation, and talkative- distinct disorders. By using the bi-modality method, a
ness) in BP-II and MDD. continuity between BP-II and MDD depressions would seem
Fig. 1 shows the Kernel density estimate distribution of the to be supported. Which of these methods for classification is the
intradepressive hypomanic symptoms rating in the entire BP-II and best has yet to be shown. At present, the study's findings seem
MDD depression sample. No bi-modality was present. to support a continuity between BP-II and MDD if Kendell and
Fig. 2 shows the histogram of the distribution of the intra- Jablensky's bi-modality method is followed. Further studies
depressive hypomanic symptoms in the entire BP-II and MDD are clearly required, in order to replicate the present study
depression sample. No bi-modality was present. findings in different settings, and to find the best method to use
for the definition of categorical mental disorders.
4. Discussion
4.4. Limitations
4.1. Differences between BP-II and MDD on diagnostic
validators A single interviewer may limit the validity of the findings.
However, the reliability of BP-II diagnosis was found to be high
Comparisons between BP-II and MDD depressions showed when trained clinicians used semi-structured interviews as in the
significant differences on several diagnostic validators, such as present study (Simpson et al., 2002). Clinicians using semi-
bipolar family history, age at onset, course (recurrences), and clinical structured interviews made more correct diagnoses of mood
picture. These findings are in line with previous reports (Angst et al., disorders, especially BP-II, compared to structured interviewing
2002; Bauer et al., 2005; Hantouche et al., 1998; McMahon et al., (Aalto-Setala et al., 2002; Brugha et al., 2001; Dunner and Tay,
1994; Mitchell and Malhi, 2004; Perugi et al., 2003; Sato et al., 1993). The interview was conducted by a clinician studying and
2003). These differences on diagnostic validators could support a treating mood disorders for a long time, systematically using
categorical distinction between BP-II depression and MDD validated structured and semi-structured instruments for each
depression, following a classic approach (Kendler, 1990). new patient, often supplemented by key informants. Assess-
ment of all consecutive patients in a systematic manner by
4.2. Lack of bi-modality between BP-II and MDD depressions validated instruments should have avoided any unintentional
systematic bias. The interviewer inter-rater reliability for the
According to Kendell and Jablensky (2003), using diagnos- diagnosis of BP-II had been shown to be acceptable (Benazzi,
tic validators is biased toward a categorical classification of 2003a). The validity of the interview method is supported by the
mental disorders. According to the same authors, the current close similarities found between a BP-II sample of the present
best approach to the categorical versus dimensional classifica- setting and a BP-II sample of an independent group (Angst et
tion would be to study if there is a bi-modality in the distribution al., 2005b). An interviewer's bias is also unlikely as the present
of some cross-sectional, distinguishing clinical features be- study aim had not been planned when the variables were
tween two related syndromes. BP-II is the closest of the bipolar collected for different study goals.
disorders to MDD. A clinical feature shown to distinguish the
depressive syndromes of BP-II and MDD is a higher frequency 4.5. Conclusions
of intradepression hypomanic symptoms in BP-II (Benazzi,
2005b; Mantere et al., 2004; Sato et al., 2003; Serretti and By using classic diagnostic validators, BP-II and MDD
Olgiati, 2005). depressions would seem to be distinct disorders. By using the
F. Benazzi / Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 10431050 1049

bi-modality method, a continuity between BP-II and MDD the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Psychol
would seem to be supported by the study's findings. Which of Med 2001;31:100113.
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